Increased expression of tenascin C by keloids in vivo and in vitro

Abstract

Tenascin C, undulin, collagen XIV and fibronectin are extracellular matrix glycoproteins with a partial DNA sequence homology. During embryogenesis, tenascin C is abundant in mesenchymal tissues but its distribution in human adult tissue is severely restricted. The levels of tenascin C expression are enhanced with skin inflammation, wound healing and hyperproliferative skin diseases and return to normal in normal scar tissue after wound contraction is completed. Undulin/collagen XIV is associated with collagen fibrils and fibronectin is present throughout the dermis in adult skin but it is produced by keloidal fibroblasts in an increased amount. In this study we investigated by immunohistochemistry the expression of the three extracellular matrix proteins in keloids and normal skin as well as in keloidal and normal fibroblasts in vitro. In keloids, increased tenascin C expression was observed especially in the reticular dermis associated with collagen fibrils sharply demarcating the limit of the lesion. In normal tissue, tenascin C was only expressed beneath the basal lamina and dermal-epidermal junction. Corresponding to the in vivo findings, tenascin C expression was increased in keloidal fibroblasts compared with normal fibroblasts in vitro (P < 0.003), whereas undulin/collagen XIV and fibronectin expression in keloids and keloidal fibroblasts was similar to that in normal tissue and normal fibroblasts, respectively. Therefore, tenascin C is a marker associated with keloids and we suggest that keloidal fibroblasts, once stimulated, continue to produce tenascin C independently from circulating factors.

Tenascins: regulation and putative functions during pathological stress

“…A small load fitted to one wing of young chickens results in stretch to the anterior latissimus dorsi (ALD) holding muscle. Within less than half a day, tenascin-C protein was induced de novo, ie ectopically, in the endomysium throughout the ALD muscle [102]. Northern blot analysis revealed that tenascin-C mRNA was upregulated in ALD after only 4 h of loading, while tenascin-Y mRNA was reduced.…”

“…Interestingly, while tenascin-C is found in normal skin only at a few sites (around dermal papillae and larger vessels) and is absent from mature bone matrix, this ECM protein is strongly and transiently induced both in remodelling bone [101] and in the dermis adjacent to skin wounds [53]. Moreover, tenascin-C expression is turned off in normal scars after wound contraction but persists in keloidal fibroblasts and hypertrophic scars [102], from where it disappears when external pressure is applied [100]. It is thus reasonable to assume that tenascin-C expression might be controlled in part by mechanical forces.…”

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

“…Tenascin-C is persistently upregulated in fibrotic disease, including keloids and photo-damaged skin. 146,147 Native full-length tenascin-C arrests fibroblast cell-cycle progression in G1 phase and promotes fibroblast migration along the fibrin-fibronectin matrices characteristic of early wounds. 148 Conversely, fragmented tenascin-C was shown to almost completely inhibit fibroblast migration.…”

Tenascin-C Splice Variant Adhesive/anti-Adhesive Effects on Chondrosarcoma Cell Attachment to Fibronectin.

“…Tenascin-C (TNC) is an oligomeric glycoprotein of the extracellular matrix (ECM) that has been found to be expressed in a variety of processes including cartilage development (Gluhak et al, 1996;Mackie and Murphy, 1998;Mackie and Ramsey, 1996;Pacifici, 1995), tissue remodeling, wound healing (Dalkowski et al, 1999;Hakkinen et al, 2000;Jones et al, 2000;Latijnhouwers et al, 1996), angiogenesis (Gassler et al, 1999;Jallo et al, 1997;Klein-Soyer et al, 1997;Kostianovsky et al, 1997;Nicolo et al, 2000; and tumorogenesis (Kalembey et al, 1997;Kurpad et al, 1995;Riedl et al, 1997;Vacca et al, 1996;Wilson et al, 1999). TNC has also been implicated in a variety of cell functions including cell adhesion and anti-adhesion, migration and metastasis (Vollmer, 1997).…”